tbuckley/cabot-search huggingface dataset:
Photothermal‐Starvation Therapy Nanomodulator Capable of Inhibiting Colorectal Cancer Recurrence and Metastasis by Energy Metabolism Reduction
Authors: Xirui Duan, Hailong Tian, Shuwen Zheng, Jianmei Zhu, Chan Li, Bo He, Lei Li, Hao Jiang, Shuaijun Lu, Yumei Feng, Gary T. Bentley, Wei Zhang, Canhua Huang, Wei Gao, Na Xie, Ke Xie
Journal: Advanced Healthcare Materials (2023)

The recurrence and metastasis of colorectal cancer (CRC) have been considered as a severe challenge in clinical treatment. Recent studies have demonstrated that matrix metalloproteinases (MMPs) and lactate can promote local tumor angiogenesis, recurrence, and metastasis. The expression of MMPs is highly dependent on energy metabolism, and lactate is considered an alternative energy source for tumor proliferation and metastasis. Therefore, using a rational approach, a photothermal-starvation therapy nanomodulator that can reduce energy metabolism to suppress CRC recurrence and metastasis is designed. To design a suitable nanomodulator, glucose oxidase (GOX), indocyanine green (IR820), and α-cyano-4-hydroxycinnamic acid (CHC) into nanoparticles by a coassembly method are combined. The photothermal properties of IR820 provide the appropriate temperature and oxygen supply for the enzymatic reaction of GOX to promote intracellular glucose consumption. CHC inhibits the expression of monocarboxylate transporter 1 (MCT1), the transporter of lactic acid into cells, and also reduces oxygen consumption and promotes the GOX reaction. Additionally, altering adenosine triphosphate synthesis to block heat shock proteins expression can be an effective means to prevent IR820-mediated photothermal therapy resistance. Thus, this dual photothermal-starvation therapy nanomodulator efficiently suppresses the recurrence and metastasis of CRC by depleting intracellular nutrients.
Therapeutic-oligonucleotides activated by nucleases (TOUCAN): A nanocarrier system for the specific delivery of clinical nucleoside analogues
Authors: Baris A. Borsa, Luiza I. Hernandez, Tania Jiménez, Chaitanya Tellapragada, Christian G. Giske, Frank J. Hernandez
Journal: Journal of Controlled Release (2023)

Nucleoside analogues have been in clinical use since 1960s and they are still used as the first therapeutic option for several cancers and viral infections, due to their high therapeutic efficacy. However, their wide clinical acceptance has been limited due to their high toxicity and severe side effects to patients. Herein, we report on a nanocarrier system that delivers nucleosides analogues in a target-specific manner, making nucleoside-based therapeutics safer and with the possibility to be used in other human conditions. This system, named, Therapeutic OligonUCleotides Activated by Nucleases" (TOUCAN) combines: i) the recognition power of oligonucleotides as substrates, ii) the use of nucleases as enzymatic biomarkers and iii) the clinical efficacy of nucleoside analogues, in a single approach. As a proof-of-concept, we report on a TOUCAN that is activated by a specific nuclease produced by bacteria and releases a therapeutic nucleoside, floxuridine. We demonstrate, for the first time, that, by incorporating a therapeutic nucleoside analogue into oligonucleotide probes, we can specifically inhibit bacterial growth in cultures. In this study, Staphylococcus aureus was selected as the targeted bacteria and the TOUCAN strategy successfully inhibited its growth with minimal inhibitory concentration (MIC) values ranging from 0.62 to 40 mg/L across all tested strains. Moreover, our results indicate that the intravenous administration of TOUCANs at a dose of 20 mg/kg over a 24-h period is a highly effective method for treating bacterial infections in a mouse model of pyomyositis. Importantly, no signs of toxicity were observed in our in vitro and in vivo studies. This work can significantly impact the current management of bacterial infections, laying the grounds for the development of a different class of antibiotics. Furthermore, it can provide a safer delivery platform for clinical nucleoside therapeutics in any human conditions, such as cancer and viral infection, where specific nuclease activity has been reported.
Nanoparticles that target the mitochondria of tumor cells to restore oxygen supply for photodynamic therapy: Design and preclinical validation against breast cancer
Authors: Xiaosheng Bai, Yan Lin, Lingyi Gong, Junfeng Duan, Xiaoduan Sun, Changguang Wang, Zerong Liu, Jun Jiang, Xiangyu Zhou, Meiling Zhou, Zhirong Zhang, Zhongbing Liu, Pei Jing, Zhirong Zhong
Journal: Journal of Controlled Release (2023)
American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID‐19 Pandemic: Version 1
Authors: Ted R. Mikuls, Sindhu R. Johnson, Liana Fraenkel, Reuben J. Arasaratnam, Lindsey R. Baden, Bonnie L. Bermas, Winn Chatham, Stanley Cohen, Karen Costenbader, Ellen M. Gravallese, Andre C. Kalil, Michael E. Weinblatt, Kevin Winthrop, Amy S. Mudano, Amy Turner, Kenneth G. Saag
Journal: Arthritis & Rheumatology (2020)

To provide guidance to rheumatology providers on the management of adult rheumatic disease in the context of the coronavirus disease 2019 (COVID-19) pandemic.A task force, including 10 rheumatologists and 4 infectious disease specialists from North America, was convened. Clinical questions were collated, and an evidence report was rapidly generated and disseminated. Questions and drafted statements were reviewed and assessed using a modified Delphi process. This included 2 rounds of asynchronous anonymous voting by e-mail and 3 webinars with the entire panel. Task force members voted on agreement with draft statements using a 1-9-point numerical scoring system, and consensus was determined to be low, moderate, or high based on the dispersion of votes. For approval, median votes were required to meet predefined levels of agreement (median values of 7-9, 4-6, and 1-3 defined as agreement, uncertainty, or disagreement, respectively) with either moderate or high levels of consensus.The task force approved 77 initial guidance statements: 36 with moderate and 41 with high consensus. These were combined, resulting in 25 final guidance statements.These guidance statements are provided to promote optimal care during the current pandemic. However, given the low level of available evidence and the rapidly evolving literature, this guidance is presented as a "living document," and future updates are anticipated.
Long-term safety and efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis: Interim analysis of the LIMMitless open-label extension trial up to 5 years of follow-up
Authors: Kim A. Papp, Andrew Blauvelt, Lluís Puig, Mamitaro Ohtsuki, Stefan Beissert, Melinda Gooderham, Ahmad Z. Amin, Jie Liu, Tianshuang Wu, Tofial Azam, Vassilis Stakias, Ramon Espaillat, Ranjeeta Sinvhal, Ahmed M. Soliman, Yinuo Pang, Michael M. Chen, Mark G. Lebwohl
Journal: Journal of the American Academy of Dermatology (2023)

Psoriasis is a chronic, inflammatory skin disease often requiring long-term therapy.To evaluate the long-term safety and efficacy of risankizumab in patients with psoriasis.LIMMitless is an ongoing phase 3, open-label extension study evaluating the long-term safety and efficacy of continuous risankizumab 150 mg every 12 weeks for adults with moderate-to-severe plaque psoriasis following multiple phase 2/3 base studies. This interim analysis assessed safety (ie, monitored treatment-emergent adverse events [TEAEs]) through 304 weeks. Efficacy assessments included determining the proportion of patients who achieved ≥90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90/100), static Physician's Global Assessment of clear/almost clear (sPGA 0/1), and Dermatology Life Quality Index of no effect on patient's life (DLQI 0/1) through 256 weeks.Among 897 patients randomized to risankizumab in the base studies, 706 were still ongoing at data cutoff. Rates of TEAEs, TEAEs leading to discontinuation, and TEAEs of safety interest were low. At week 256, 85.1%/52.3% of patients achieved PASI 90/100, respectively, 85.8% achieved sPGA 0/1, and 76.4% achieved DLQI 0/1.Open-label study with no placebo or active-comparator group.Long-term continuous risankizumab treatment for up to 5 years was well tolerated and demonstrated high and durable efficacy.
Robotic Kidney Transplantation with Regional Hypothermia: Evolution of a Novel Procedure Utilizing the IDEAL Guidelines (IDEAL Phase 0 and 1)
Authors: Mani Menon, Ronney Abaza, Akshay Sood, Rajesh Ahlawat, Khurshid R. Ghani, Wooju Jeong, Vijay Kher, Ramesh K. Kumar, Mahendra Bhandari
Journal: European Urology (2013)
Targeting impaired nutrient sensing via the sirtuin pathway with novel compounds to prevent or treat dementia: A systematic review
Authors: Adrian Matysek, Lina Sun, Sumudu Perera Kimmantudawage, Lei Feng, Andrea B. Maier
Journal: Ageing Research Reviews (2023)

Dementia is prevalent in aged populations and is associated with disability and distress for those affected. Therapeutic benefits of drugs targeting dementia are small. Impaired nutrient sensing pathways have been implicated in the pathogenesis of dementia and may offer a novel treatment target. This systematic review collated evidence for novel therapeutic compounds that modify nutrient sensing pathways, particularly the sirtuin pathway, in preventing cognitive decline or improving cognition in normal ageing, mild cognitive impairment (MCI), and dementia. PubMed, Embase and Web of Science databases were searched using key search terms. Articles were screened using Covidence systematic review software. The risk of bias was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE)'s risk of bias tool for animal studies and Cochrane Risk of Bias tool v 2.0 for human studies. Out of 3841 articles, 68 were included describing 38 different novel therapeutic compounds that modulate the nutrient sensing pathway via the sirtuin pathway. In animal models (58 studies), all investigated novel therapeutic compounds showed cognitive benefits. Ten studies were human intervention trials targeting normal ageing (1 study) and dementia populations (9 studies). Direct sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1) activators Resveratrol and Nicotinamide derivatives improved cognitive outcomes among human subjects with normal cognition and MCI. Animal studies support that modulation of the sirtuin pathway has the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations.
European candidaemia is characterised by notable differential epidemiology and susceptibility pattern: Results from the ECMM Candida III study
Authors: Maiken Cavling Arendrup, Sevtap Arikan-Akdagli, Karin Meinike Jørgensen, Aleksandra Barac, Jörg Steinmann, Cristina Toscano, Valentina Arsic Arsenijevic, Assunta Sartor, Cornelia Lass-Flörl, Axel Hamprecht, Tadeja Matos, Benedict R.S. Rogers, Inmaculada Quiles, Jochem Buil, Volkan Özenci, Robert Krause, Matteo Bassetti, Laura Loughlin, Blandine Denis, Anna Grancini, P. Lewis White, Katrien Lagrou, Birgit Willinger, Riina Rautemaa-Richardson, Petr Hamal, Beyza Ener, Tugce Unalan-Altintop, Ebru Evren, Suleyha Hilmioglu-Polat, Yasemin Oz, Ozlem Koyuncu Ozyurt, Faruk Aydin, Filip Růžička, Eelco F.J. Meijer, Jean Pierre Gangneux, Deborah E.A. Lockhart, Nina Khanna, Clare Logan, Ulrike Scharmann, Guillaume Desoubeaux, Emmanuel Roilides, Alida Fe Talento, Karin van Dijk, Philipp Koehler, Jon Salmanton-García, Oliver A. Cornely, Martin Hoenigl
Journal: Journal of Infection (2023)
Single-cell sequencing on CD8<sup>+</sup>TILs revealed the nature of exhausted T cells recognizing neoantigen and cancer/testis antigen in non-small cell lung cancer
Authors: Hiroyasu Komuro, Shuichi Shinohara, Yasunori Fukushima, Ayako Demachi-Okamura, Daisuke Muraoka, Katsuhiro Masago, Takuya Matsui, Yusuke Sugita, Yusuke Takahashi, Reina Nishida, Chieko Takashima, Takashi Ohki, Yoshiki Shigematsu, Fumiaki Watanabe, Katsutoshi Adachi, Takashi Fukuyama, Hiroshi Hamana, Hiroyuki Kishi, Daiki Miura, Yuki Tanaka, Kousuke Onoue, Kazuhide Onoguchi, Yoshiko Yamashita, Richard Stratford, Trevor Clancy, Rui Yamaguchi, Hiroaki Kuroda, Kiyoshi Doi, Hisashi Iwata, Hirokazu Matsushita
Journal: Journal for ImmunoTherapy of Cancer (2023)

CD8+tumor infiltrating lymphocytes (TILs) are often observed in non-small cell lung cancers (NSCLC). However, the characteristics of CD8+ TILs, especially T-cell populations specific for tumor antigens, remain poorly understood. High throughput single-cell RNA sequencing and single-cell T-cell receptor (TCR) sequencing were performed on CD8+ TILs from three surgically-resected lung cancer specimens. Dimensional reduction for clustering was performed using Uniform Manifold Approximation and Projection. CD8+ TIL TCR specific for the cancer/testis antigen KK-LC-1 and for predicted neoantigens were investigated. Differentially-expressed gene analysis, Gene Set Enrichment Analysis (GSEA) and single sample GSEA was performed to characterize antigen-specific T cells. A total of 6998 CD8+ T cells was analyzed, divided into 10 clusters according to their gene expression profile. An exhausted T-cell (exhausted T (Tex)) cluster characterized by the expression of ENTPD1 (CD39), TOX, PDCD1 (PD1), HAVCR2 (TIM3) and other genes, and by T-cell oligoclonality, was identified. The Tex TCR repertoire (Tex-TCRs) contained nine different TCR clonotypes recognizing five tumor antigens including a KK-LC-1 antigen and four neoantigens. By re-clustering the tumor antigen-specific T cells (n=140), it could be seen that the individual T-cell clonotypes were present on cells at different stages of differentiation and functional states even within the same Tex cluster. Stimulating these T cells with predicted cognate peptide indicated that TCR signal strength and subsequent T-cell proliferation and cytokine production was variable but always higher for neoantigens than KK-LC-1. Our approach focusing on T cells with an exhausted phenotype among CD8+ TILs may facilitate the identification of tumor antigens and clarify the nature of the antigen-specific T cells to specify the promising immunotherapeutic targets in patients with NSCLC.
Emerging strategies to bypass transplant rejection via biomaterial-assisted immunoengineering: Insights from islets and beyond
Authors: Samin Abbaszadeh, Vahideh Nosrati-Siahmazgi, Kiyan Musaie, Saman Rezaei, Mostafa Qahremani, Bo Xiao, Hélder A. Santos, Mohammad-Ali Shahbazi
Journal: Advanced Drug Delivery Reviews (2023)

Novel transplantation techniques are currently under development to preserve the function of impaired tissues or organs. While current technologies can enhance the survival of recipients, they have remained elusive to date due to graft rejection by undesired in vivo immune responses despite systemic prescription of immunosuppressants. The need for life-long immunomodulation and serious adverse effects of current medicines, the development of novel biomaterial-based immunoengineering strategies has attracted much attention lately. Immunomodulatory 3D platforms can alter immune responses locally and/or prevent transplant rejection through the protection of the graft from the attack of immune system. These new approaches aim to overcome the complexity of the long-term administration of systemic immunosuppressants, including the risks of infection, cancer incidence, and systemic toxicity. In addition, they can decrease the effective dose of the delivered drugs via direct delivery at the transplantation site. In this review, we comprehensively address the immune rejection mechanisms, followed by recent developments in biomaterial-based immunoengineering strategies to prolong transplant survival. We also compare the efficacy and safety of these new platforms with conventional agents. Finally, challenges and barriers for the clinical translation of the biomaterial-based immunoengineering transplants and prospects are discussed.
Magnetic‐Based Strategies for Regenerative Medicine and Tissue Engineering
Authors: Lúcia F. Santos, Ana S. Silva, João F. Mano
Journal: Advanced Healthcare Materials (2023)

The fabrication of biological substitutes to repair, replace, or enhance tissue- and organ-level functions is a long-sought goal of tissue engineering (TE). However, the clinical translation of TE is hindered by several challenges, including the lack of suitable mechanical, chemical, and biological properties in one biomaterial, and the inability to generate large, vascularized tissues with a complex structure of native tissues. Over the past decade, a new generation of "smart" materials has revolutionized the conventional medical field, transforming TE into a more accurate and sophisticated concept. At the vanguard of scientific development, magnetic nanoparticles (MNPs) have garnered extensive attention owing to their significant potential in various biomedical applications owing to their inherent properties such as biocompatibility and rapid remote response to magnetic fields. Therefore, to develop functional tissue replacements, magnetic force-based TE (Mag-TE) has emerged as an alternative to conventional TE strategies, allowing for the fabrication and real-time monitoring of tissues engineered in vitro. This review addresses the recent studies on the use of MNPs for TE, emphasizing the in vitro, in vivo, and clinical applications. Future perspectives of Mag-TE in the fields of TE and regenerative medicine are also discussed.
Sequential Therapy versus Standard Triple-Drug Therapy for <i>Helicobacter pylori</i> Eradication
Authors: Dino Vaira, Angelo Zullo, Nimish Vakil, Luigi Gatta, Chiara Ricci, Federico Perna, Cesare Hassan, Veronica Bernabucci, Andrea Tampieri, Sergio Morini
Journal: Annals of Internal Medicine (2007)

Background: Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. Objective: To determine whether sequential treatment eradicates H. pylori infection better than standard triple-drug therapy for adults with dyspepsia or peptic ulcers. Design: Randomized, double-blind, placebo-controlled trial. Setting: Two Italian hospitals between September 2003 and April 2006. Patients: 300 patients with dyspepsia or peptic ulcers. Measurements: 13C-urea breath test, upper endoscopy, histologic evaluation, rapid urease test, bacterial culture, and assessment of antibiotic resistance. Intervention: A 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, and placebo, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or standard 10-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily). Results: The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the standard treatment in the intention-to-treat analysis (89% vs. 77%; P = 0.0134; difference, 12% [95% CI, 3% to 20%]), the modified intention-to-treat analysis (91% vs. 78%; P = 0.0022; difference, 13% [CI, 5% to 21%]), and the per-protocol analysis (93% vs. 79%; P = 0.0013; difference, 14% [CI, 6% to 21%]). Sequential therapy was significantly more effective in patients with clarithromycin-resistant strains (89% vs. 29%; P = 0.0034). The incidence of major and minor side effects did not differ between therapy groups (17% in both groups). One patient (0.7%) in the standard therapy group discontinued treatment because of side effects. Limitations: Follow-up was incomplete in 4.6% and 2.7% patients in the sequential therapy and standard therapy groups, respectively. The results may not be generalizable to other countries. Sequential therapy may be more effective because it includes 1 additional antibiotic (tinidazole) that is not contained in standard therapy. Conclusions: Sequential therapy is statistically significant compared with standard therapy for eradicating H. pylori infection and is statistically significantly more effective in patients with clarithromycin-resistant strains. Side effects are similar with both treatment regimens and are rarely severe enough to cause discontinuation of therapy. ClinicalTrials.gov registration number: NCT00403364.
Estimation of True Calcium Absorption
Authors: ROBERT P. HEANEY
Journal: Annals of Internal Medicine (1985)

Measurements of true calcium absorption fraction in women were evaluated to see how closely calculations based on a single measurement of serum specific activity after administration of an oral calcium tracer might approximate the absorption value derived from the full, double-isotope absorption procedure. True absorption, body size, and miscible pool turnover could together explain better than 93% of the variance in serum calcium specific activity values 5 hours after a tracer-labeled test meal. Because measurement of pool turnover is not available routinely, it was dropped from the model, and a predictor equation was developed that allowed estimation of true absorption from the 5-hour serum specific activity value, height, and weight. These variables explained 90.8% of the variance in the 5-hour values and gave estimates of true absorption with a 95% confidence interval of ±0.055. This small range of uncertainty makes the procedure useful in estimating absorption efficiency for calcium therapy in routine clinical practice.
Mediterranean diet and olive oil, microbiota, and obesity-related cancers. From mechanisms to prevention
Authors: Enrique Almanza-Aguilera, Ainara Cano, Mercedes Gil-Lespinard, Nerea Burguera, Raul Zamora-Ros, Antonio Agudo, Marta Farràs
Journal: Seminars in Cancer Biology (2023)

Olive oil (OO) is the main source of added fat in the Mediterranean diet (MD). It is a mix of bioactive compounds, including monounsaturated fatty acids, phytosterols, simple phenols, secoiridoids, flavonoids, and terpenoids. There is a growing body of evidence that MD and OO improve obesity-related factors. In addition, obesity has been associated with an increased risk for several cancers: endometrial, oesophageal adenocarcinoma, renal, pancreatic, hepatocellular, gastric cardia, meningioma, multiple myeloma, colorectal, postmenopausal breast, ovarian, gallbladder, and thyroid cancer. However, the epidemiological evidence linking MD and OO with these obesity-related cancers, and their potential mechanisms of action, especially those involving the gut microbiota, are not clearly described or understood. The goals of this review are 1) to update the current epidemiological knowledge on the associations between MD and OO consumption and obesity-related cancers, 2) to identify the gut microbiota mechanisms involved in obesity-related cancers, and 3) to report the effects of MD and OO on these mechanisms.